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Hair Loss Study Abstract: Evaluation of RU58841 as an anti-androgen in prostate PC3 cells and a topical
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Title
Evaluation of RU58841 as an anti-androgen in prostate PC3
cells and a topical anti-alopecia agent in the bald scalp of stumptailed macaques.
Author
Pan HJ; Wilding G; Uno H; Inui S; Goldsmith L; Messing E;
Chang C
Address
Department of Pathology, University of Rochester Medical
Center, NY 14642, USA.
Source
Endocrine, 9(1):39-43 1998 Aug
Abstract
The effect of androgen receptor transcriptional activation by
RU58841, a nonsteroidal anti-androgen, was studied in the human prostate cancer PC3 cell
line by cotransfection with wild-type androgen receptor (wt AR) and an androgen-responsive
reporter (MMTV-ARE-CAT) construct. Anti-and rogens, hydroxyflutamide, and Casodex, and the
antiestrogen, genistein, were studied in parallel for comparison with RU58841. The wt AR
was activated only by the androgen dihydrotestosterone (DHT). Neither the anti-androgens
nor antiestrogen can enhance AR transcriptional activity at 10(-11)-10(-7)M in PC3 cells.
Hydroxyflutamide, RU58841, and Casodex, but not genistein, displayed competitively
suppressive effects on DHT activation of wt AR. The potency of RU58841 was comparable to
that of hydroxyflutamide. From this result, topical application of RU58841, which is
considered to be a potential therapy for skin diseases, may induce systemic side effects.
However, RU58841, on topical application, revealed a potent increase in density,
thickening, and length of hair in the macaque model of androgenetic
alopecia, whereas no systemic effects were detected. Together our results suggest that
RU58841 may have potent antagonism to the wt AR and could be considered as a topically
applied active anti-androgen for the treatment of androgen-dependent skin disorders, such
as acne, androgenetic alopecia, and hirsutism.
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